Steroid hormones act via specific receptor proteins to exert profound effects on the development and physiological regulation of virtually every animal tissue. We propose in this application to investigate the molecular biology of glucocorticoid action in tissue culture lines derived from lymphosarcoma, hepatoma and mammary carcinoma cells. Mammary tumor virus genes selectively respond to glucocorticoid stimulation; techniques involving restriction endonucleases and molecular cloning would be employed to examine in detail sequences involved in hormonal responsiveness of these genes. Various procedures employing specific molecular hybridization and immunochemical probes would be employed to develop genetic mutants defective in the steroid response. These mutants would be used to identify the molecular components involved in hormone action, to define complementation groups by somatic cell hybridization techniques and to act as genetic controls in correlating biochemical observations with in vivo events.